xerostomia

Name of the Trial
Randomized Pilot Study of Electroacupuncture for Chronic Radiation-induced Xerostomia in Patients with Head and Neck Cancer (MAYO-MCS285). See the protocol summary 1.

Why This Trial Is Important
Head and neck cancers are often treated with external-beam radiation therapy 2. Although this treatment can be effective in controlling head and neck tumors, it may cause side effects 3 that can compromise a patient’s quality of life. Chronic dry mouth, also called xerostomia, is common among patients treated with radiation to the head and neck. This condition results from damage to the glands that produce saliva. Chronic dry mouth can have a major impact 4 on quality of life by causing pain and discomfort, affecting the ability to sleep, altering taste, and/or increasing the likelihood of dental problems.

Some drugs are available for xerostomia induced by radiation therapy, but many patients experience only a partial improvement or no benefit at all. The drug amifostine 5 can help protect the salivary glands of some head and neck cancer patients from radiation damage, but this drug cannot be used in all patients.

Some studies have suggested that acupuncture 6 can help relieve the sensation of mouth dryness in cancer patients who have undergone head and neck radiation therapy. Based on these studies and other evidence, researchers at the Mayo Clinic in Scottsdale, AZ, are investigating the ability of a procedure called electroacupuncture to help improve the production of saliva and the quality of life of patients with chronic dry mouth. Electroacupuncture involves stimulating traditional acupuncture points 7 on the skin using small electrodes instead of needles inserted into the skin.

In this clinical trial, head and neck cancer patients with chronic dry mouth who completed radiation therapy at least 6 months before joining the trial and who received no benefit from treatment with the drug pilocarpine 8 (Salagen) will be randomly assigned to undergo electroacupuncture using a machine called a LISS stimulator, or a sham procedure using a similar-looking machine that does not produce electrical stimulation. Treatment will last for 4 weeks (20-minute sessions 5 days a week for the first 2 weeks, and then 3 days a week for the last 2 weeks) and will be administered at the Mayo Clinic in Scottsdale. Saliva flow, the patients’ subjective sensation of mouth dryness, and quality of life will be assessed during the first 3 weeks of treatment and then again 1, 3, and 6 months following treatment.

“Depending on the radiation techniques used and the location of the tumor, up to 90 percent of head and neck cancer patients receiving radiation therapy will experience chronic dry mouth,” said Dr. Halyard. “Electroacupuncture is a non-needle approach that uses electrical stimulation of the acupuncture points thought to control salivation. The hypothesis is that this stimulation will alter the energy flow of the acupuncture points and result in an increase in saliva production.

“To date, we have enrolled 24 of 30 patients for the study, so we have 6 slots left,” Dr. Halyard continued. “I would be happy to discuss the study with any patients who think they might be interested and who can commit a month to treatment in Scottsdale, as well as return for the three post-treatment assessments.” (See contact information link.)

June 1, 2010 — Intensity-modulated radiation therapy (IMRT) for head and neck cancer leads to fewer cases of xerostomia, but has not yet been proven to be more successful than any other kind of radiation therapy in reducing tumors or improving survival, according to a new comparative-effectiveness review funded by the federal Agency for Healthcare Research and Quality (AHRQ).

Many scientists consider IMRT to be theoretically better able to target cancerous cells while sparing healthy tissue than either 3DCRT or 2DRT, but more research is needed, the authors of the report point out.

The late adverse effect of xerostomia, also known as dry mouth, is less common than in the past because the use of IMRT has allowed radiation oncologists to spare most patients’ salivary glands from radiation as part of treatment planning, an expert recently toldMedscape Oncology.

Sparing salivary glands has become standard among clinicians who use IMRT, said Avraham Eisbruch, MD, professor of radiation oncology at the University of Michigan Medical School and Comprehensive Cancer Center in Ann Arbor.

Dr. Eisbruch’s comments came in the context of his study on the use of IMRT to reduce dysphagia in head and neck cancer. However, he also served on the technical expert panel of the new comparative-effectiveness report.

According to the report, it is not known whether IMRT is better or worse at reducing the size of tumors, or whether it improves other outcome measures.

“Inconsistent and nonsignificant results were observed between IMRT and comparators on other adverse events, overall quality of life, tumor control, and survival outcomes. Thus, the evidence is insufficient to support conclusions in these areas,” reads the report.

Overall, the report suffered from a lack of data with which to do comparisons, suggest the authors.

“A small body of randomized, controlled trials is accompanied by a larger body of poor quality observational, nonrandomized studies,” they write about the evidence on the topic.

What About Proton-Beam Therapy?

The main focus of the report was IMRT. An informal survey estimates that 30% to 60% of all patients in the United States are treated with IMRT.

The report authors note that “most of the studies in this review were based on the results of patients treated at academic medical centers.”

Because IMRT is increasingly adopted in community settings, the authors wonder whether results in head and neck cancer will continue to be the same.

“Whether similar results will be achieved as the technology diffuses to less-experienced settings has not been addressed in the comparative studies available for this review,” they write.

The authors sought to examine the evidence regarding proton beam radiation therapy, but there were no head-to-head comparisons to review.

“The strength of evidence is insufficient, as there were no studies comparing proton-beam therapy to any other radiotherapy modality. Therefore, no conclusions can be reached regarding the comparative effectiveness of proton-beam therapy,” write the authors.

Proton-beam radiation therapy is more commonly used to treat prostate cancer and pediatric tumors, the report notes.

In an AHRQ Technical Brief published last fall, researchers found limited evidence with which to determine whether proton-beam radiation therapy is safer or more effective than other types of radiation to treat cancer, according to AHRQ press materials.

The new comparative-effectiveness report is the latest research review from the AHRQ’s Effective Health Care Program, which is an effort to compare alternative treatments for health conditions and to make the findings public, to help doctors, nurses, pharmacists, and others work together with patients to choose the most effective treatments.

An advanced type of cancer radiation is more successful than traditional radiation in avoiding “dry mouth” when treating head and neck cancers, but it is unknown whether the treatment is better or worse at reducing the size of tumors, according to a new comparative effectiveness review funded by HHS’ Agency for Healthcare Research and Quality.

The report finds that intensity-modulated radiation therapy (IMRT) leads to fewer cases of xerostomia, commonly known as dry mouth, than other types of radiation. Xerostomia, a potential side effect to radiation when salivary glands are damaged, can affect basic functions like chewing, swallowing and breathing; senses such as taste, smell and hearing; and can significantly alter a patient’s appearance and voice.

However, the report did not find evidence that IMRT is more successful than any other kind of radiation therapy in reducing tumors. Many scientists consider IMRT to be theoretically better able to target cancerous cells while sparing healthy tissues, but more research is needed, the report said. The comparative effectiveness review, Comparative Effectiveness and Safety of Radiotherapy Treatments for Head and Neck Cancer, was authored by the Blue Cross and Blue Shield (BC/BS) Association, Technology Evaluation Center in Chicago.

“The development of new technologies to treat cancer has been one of the true success stories of American medical research,” said AHRQ Director Carolyn M. Clancy, M.D. “This report provides patients and their doctors with more information about these advances, which they can use to make more informed choices about their own treatment.”

The report examines treatment for cancers to the head and neck, including the mouth, larynx and sinuses. (Tumors in the brain are considered a separate type of cancer and are not discussed in this report.) Non-brain head and neck cancers account for up to 5 percent of cancers that are diagnosed in the United States, with an estimated 47,560 new cases and 11,260 deaths in 2008.

As with other cancers, head and neck cancer often is treated by radiation, which can damage both cancerous and non-cancerous cells. To limit damage to non-cancerous cells, scientists have sought ways to target high doses of radiation to cancerous cells while sparing healthy ones. This is particularly important with head and neck cancers, because tumors can reside close to vital organs.

Standard radiation therapy has evolved over the past 20 years and now provides doctors with two- or three-dimensional images that simulate a patient’s treatment area on a computer screen. IMRT, which has been implemented over the past 10 years, also employs three-dimensional imaging and further technological and treatment enhancements that tightly control and target the amount of radiation delivered to the target area.

A newly developed time-released muco-adhesive patch for treating oral health conditions, including the widespread condition of dry mouth (xerostomia), has been shown to be more effective than a leading oral rinse, according to a newly-published study. As increasing segments of the population consume more medications (one of the leading causes of dry mouth), the results of this study could potentially help provide relief for millions of Americans. Chronic dry mouth impacts the quality of life and for some, can be debilitating. Published in the March 2010 issue of Quintessence International, the study found that chronic dry mouth sufferers can now get a statistically significant reduction of mouth dryness from a new time-released muco-adhesive patch (OraMoist Dry Mouth Patch), compared with the leading oral rinse which has been on the market for nearly two decades.

Overall, patients with xerostomia treated with the muco-adhesive patch reported a statistically significant reduction in mouth dryness sensation with elevated salivary flow rate (150%) after just 30 minutes, which was considered clinically outstanding by the study authors, since the product does not contain any cholinergic agonist, a drug often used to treat dry mouth.

OraMoist, a new time-released, non-drug formula, not only outperformed the mouthwash, one of the most often used delivery formats for treating dry mouth, but unlike dry mouth sprays, rinses or gels, which need to be applied frequently – sometimes every 20 minutes – OraMoist works to increase moisture and help restore a healthy oral environment for hours at a time, day or night, and can even be used by those with dental appliances, such as dentures. It moistens and lubricates the mouth with time-released lipids, citrus oil and sea salt, while simultaneously stimulating saliva production and inhibiting bacterial growth and promoting oral health with enzymes and xylitol.

“Oral disorders such as dry mouth and canker sores require long residence of the active remedy in the mouth or the disease site for effective treatment. Muco-adhesive patches made of safe ingredients that adhere to the oral mucosal tissue and slowly erode while releasing active remedies for two to six hours provide the desired residence time for effective therapy,” said Professor Abraham J. Domb, PhD, Institute of Drug Research, School of Pharmacy, Faculty of Medicine at the Hebrew University, co-author of the new published study, inventor of the muco-adhesive time-released patch and world-renowned for his work in biodegradable polymers. “This novel approach of time-released delivery has proven to be a successful and desirable approach to treating chronic conditions that affect millions of people, and can be disruptive to their lifestyle.”

The evolution of the muco-adhesive patch has found commercial viability in treating canker sores as well because the patch can also act as a bandage for the sores for eight to twelve hours while releasing active remedial ingredients.

Dry mouth affects upwards of 17% of the population, increasing in older adults (65 years and older) to about 30%. In fact, 34% of people taking three or more medications suffer from dry mouth, which is also a chronic symptom of numerous medical conditions, such as diabetes and Sjogren’s Syndrome.

Clinical studies suggest that advanced treatments like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) are enabling radiation oncologists to enhance post-treatment health-related quality of life for patients with head and neck cancer.

In an educational session for radiotherapy professionals, delivered by two noted experts during the annual meeting of the American Society for Radiation Oncology (ASTRO) in Chicago last week, Avraham Eisbruch, M.D., professor at the University of Michigan, discussed how careful implementation of IMRT in the treatment of head and neck cancer can achieve high tumor control rates while minimizing xerostomia, a dry mouth condition that occurs when salivary glands are damaged.

Citing a new report summarizing results from RTOG 0022, a multi-institutional study comparing IMRT with earlier forms of treatment for head and neck cancer, Dr. Eisbruch said that IMRT for head and neck cancer achieved important goals in reducing treatment toxicity, notably xerostomia, and in yielding a high tumor control rate of 90%.(1)

For patients enrolled in the study and treated with IMRT, only 55% experienced Grade 2 or worse xerostomia at six months after treatment, as compared with 84% of patients treated with earlier forms of radiotherapy — a reduction of 35%. For the IMRT group, the percentage of patients with Grade 2 or worse xerostomia decreased steadily, to 25% at 12 months and 16% at 24 months. “This kind of improvement over time is not something we had been seeing with conventional forms of radiotherapy,(2)” said Dr. Eisbruch, who served as chair of RTOG 0022.

“Also, emerging data is suggesting that we can get improvements in broader aspects of post-treatment quality of life by using IMRT, beyond reducing xerostomia,” Eisbruch said. “Several studies comparing IMRT with conventional radiotherapy found that the IMRT patients did better not just in terms of dry mouth, but also other quality of life dimensions, including swallowing and nutrition.”(3)(4)(5)

According to Eisbruch, RTOG 0225, another multi-institutional study looked at IMRT with or without chemotherapy for head and neck cancer, and also reached positive conclusions. “That group reproduced the excellent results that individual treatment centers had been reporting, namely, a 90% loco-regional progression-free survival with minimal grade 3 and no grade 4 xerostomia.”(6)

IMRT involves shaping radiotherapy treatment beams so that they deliver a dose pattern that matches the size and shape of a targeted tumor while minimizing exposure of surrounding healthy tissues and organs. This approach has been widely adopted by radiation oncologists for the treatment of diverse forms of cancer. Ongoing clinical studies are now maturing, allowing long term outcomes to be assessed and validating IMRT based on clinical data.

Improving IMRT Through Image-Guidance
Lei Dong, PhD, associate professor of medical physics at the MD Anderson Cancer Center in Houston, Texas, detailed how new image-guidance technologies further enhance the accuracy of IMRT treatments by enabling clinicians to correct for patient set-up uncertainties and anatomical changes over a course of treatment.

“Clinicians naturally want to take advantage of the more conformal dose distributions that IMRT makes possible by reducing the treatment margins around a tumor, to protect more healthy tissues,” said Dr. Dong. “When we do that, it is important to ensure that the treatments are targeted very precisely, so the tumor receives the high dose treatments, and the dose to surrounding tissues and organs is kept as low as possible.”

Dr. Dong discussed the issue of basing radiotherapy treatment plans on single CT scans taken during treatment simulation. “Internal motion can affect the accuracy of tumor definition if the CT scan is acquired while the patient is swallowing,” he said, referencing a study he worked on with colleagues from M. D. Anderson Cancer Center.(7)

According to Dr. Dong, stereoscopic X-ray imaging and volumetric cone-beam CT imaging, two imaging techniques enabled by Varian’s On-Board Imager® kV imaging device, make it possible to fine-tune patient positioning just prior to each daily treatment. In addition, frequent imaging can alert clinicians to changes in a patient’s anatomy over time, so that a new treatment plan can be developed part-way through a course of treatment whenever warranted–a process called adaptive radiotherapy.

“Preliminary studies have shown that combining IGRT and adaptive IMRT replanning can improve the overall quality of the treatment plan and, most importantly, reduce unnecessary doses to normal organs surrounding the tumor, such as the parotid glands and oral cavities,” Dr. Dong said.(8) “Combining IGRT with IMRT creates a powerful tool for high precision radiation therapy.”

“IMRT treatment was described as ‘boosted’ because we use 2 different doses in the same patient, who gets a dose of 2.12 gy to 1 part of their anatomy, while another part gets 1.8 gy,” said Sebastien Clavel, MD, University of Montreal, Montreal, Quebec, on November 3 at the American Society of Therapeutic Radiology and Oncology (ASTRO) 51st Annual Meeting.

In the study, 249 patients with stage III and IV oropharyngeal carcinoma were treated between 2000 and 2007. Of these, 100 received IMRT, while 149 patients received conventional radiation therapy.

After a 33-month median follow-up, 95.4% of those treated with IMRT were still alive, compared with 75.8% of those in the conventional arm. Disease-free survival was 89.3% for the IMRT group, compared with 71.6% in the conventional radiation arm. In addition, local control was 92.4% in the IMRT patients, compared with 85.3% in the conventional group.

“With the old technique, the rays were shooting from both sides, whereas with IMRT, the rays come from all directions,” said Dr. Clavel. “When using IMRT, we also always give them a 3-mm margin with the skin, both of which result in fewer cases of dermatitis.” IMRT patients experienced a 20% decrease in dermatitis grades 3 and 4.

“If we are able to treat the tumour with IMRT while avoiding the structure of the parotid gland, which produces saliva, the patients can live better, because more saliva is useful to protect the teeth, to eat, and swallow,” he added, noting that only 8% of those treated with IMRT experience grade 3 or 4 xerostomia at 2 years following treatment, compared with 80% of those treated with conventional radiation.

Better salivary function was also associated with increased weight regain post operatively. “Patients lost 10% of their weight during treatment; while they did not gain all their weight back in the IMRT group, they were able to regain up to 50% more than those treated with conventional radiation,” said Dr. Clavel.

In evaluating the effect of cepharanthin on and taste disorder in 40 patients undergoing radiotherapy for head and neck cancer, we administered cepharanthin intravenously during chemoradiotherapy to 22 patients, with 18 others as a control group. Cepharanthin did not significantly affect salivary secretion during and after chemoradiotherapy, although taste disorder and oral discomfort were alleviated. Cepharanthin may thus be effective in maintaining the quality of life of patients with head and neck cancer.

Background:
A distressing complication of radiotherapy treatment for head and neck cancer is xerostomia (chronic oral dryness). Xerostomia is difficult to treat conventionally but there are reports that acupuncture can help. We conducted a feasibility study to examine the acceptability of a standardised group acupuncture technique and adherence to group sessions, together with acceptability of the objective and subjective measurements of xerostomia.

Methods:
12 males with established radiation induced xerostomia were treated in three groups of four. Each received eight weekly sessions of acupuncture using four bilateral acupuncture points (Salivary Gland 2; Modified Point Zero; Shen Men and one point in the distal radial aspect of each index finger (LI1)). Sialometry and quality of life assessments were performed at baseline and at the end of treatment. A semi-structured interview was conducted a week after completing the intervention.

Results:
Adherence to and acceptability of the treatment and assessments was 100%. There were objective increases in the amounts of saliva produced for 6/12 patients post intervention and the majority also reported subjective improvements. Mean quality of life scores for domains related to salivation and xerostomia also showed improvement. At baseline 92% (11/12) patients reported experiencing a dry mouth “quite a bit/very much” as compared to 42% (5/12) after the treatment. Qualitative data revealed that the patients enjoyed the sessions.

Conclusion: The pilot study shows that a standardised group technique is deliverable and effective. The tools for objective and subjective assessment are appropriate and acceptable. Further examination in a randomised trial is now warranted.

In head and neck cancer, bilateral neck irradiation is the standard approach for many tumor locations and stages. Increasing knowledge on the pattern of nodal invasion leads to more precise targeting and normal tissue sparing.

The aim of the present study was to evaluate the morbidity and tumor control for patients with well lateralized squamous cell carcinomas of the oral cavity and oropharynx treated with ipsilateral radiotherapy.

Methods:
Twenty consecutive patients with lateralized carcinomas of the oral cavity and oropharynx were treated with a prospective management approach using ipsilateral irradiation between 2000 and 2007. This included 8 radical oropharyngeal and 12 postoperative oral cavity carcinomas, with Stage T1-T2, N0-N2b disease.

The actuarial freedom from contralateral nodal recurrence was determined. Late xerostomia was evaluated using the European Organization for Research and Treatment of Cancer QLQ-H&N35 questionnaire and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.

Results:
At a median follow-up of 58 months, five-year overall survival and loco-regional control rates were 82.5% and 100%, respectively.

No local or contralateral nodal recurrences were observed. Mean dose to the contralateral parotid gland was 4.72 Gy and to the contralateral submandibular gland was 15.30 Gy.

Mean score for dry mouth was 28.1 on the 0-100 QLQ-H&N35 scale. According to CTCAE v3 scale, 87.5% of patients had grade 0-1 and 12.5% grade 2 subjective xerostomia.

The unstimulated salivary flow was >0.2 ml/min in 81.2% of patients and 0.1-0.2 ml/min in 19%. None of the patients showed grade 3 xerostomia.

Conclusions:
In selected patients with early and moderate stages, well lateralized oral and oropharyngeal carcinomas, ipsilateral irradiation treatment of the primary site and ipsilateral neck spares salivary gland function without compromising loco-regional control.

Although the mechanisms underlying abnormalities in the senses of taste and smell in cancer patients are unknown, such disturbances clearly decrease quality of life for the majority of cancer patients—and clinicians need to be aware of the problem in order to help a person’s recovery.

This is the word from a study recently published in The Journal of Supportive Oncology (2009;7:58-65). Jae Hee Hong, PhD, Pinar Omur-Ozbek, PhD, Brian T. Stanek, and coinvestigators from Wake Forest University Comprehensive Cancer Center and Virginia Tech’s food science and technology department and biomedical engineering school conclude, “Oncologists who understand the types and causes of taste and olfactory abnormalities may be better prepared to discuss and empathize with these negative side effects.”

Altered sensory perception can undermine a person’s struggle against cancer by causing malnutrition and anxiety. One study cited by Dr Hong and colleagues found that malnutrition, not malignancy, was the primary cause of morbidity in 20% of cancer patients.

Dr Hong and colleagues explain that disorders of taste and odor can result from cancer itself or from cancer treatments, with 68% of chemotherapy patients reporting such problems. But the specific causes of these alterations often remain unidentified.

How Senses Go Bad
According to the researchers, problems with taste and smell break down into 3 categories: loss of sensitivity, distorted perception, and hallucination. The abnormalities may take the following forms:

• absence of taste perception (ageusia) or odor perception (anosmia)
• reduced sensitivity to taste perception (hypogeusia) or odor perception (hyposmia)
• distortion of taste perception (dysgeusia) or odor perception, with the person being unable to identify odors (dysosmia); in dysosmia, the person may think he or she smells something when no odor is present (phantosmia), be unable to tell the difference between perceived odors (agnosia), or have altered odor perception when 1 scent is present with another (parosmia)
• perception of taste even when no substance has been ingested (phantogeusia); although the perceived taste is often described as metallic or salty, some patients have described it as bitter, sweet, sour, peppery, greasy, soapy, powdery, or chemical.

Taste Complaints Common in Patients with Head-and-Neck Cancer
Changes in taste acuity—ageusia and hypogeusia— depend on the site of the tumor, but people with head and neck cancer report more problems than do people with breast cancer or lung cancer. According to studies cited by Dr Hong’s group, approximately 85% of patients undergoing radiation treatment of the head and neck experienced unpleasant taste changes.

“Irradiation of the taste buds frequently leads to partial or complete loss of taste or alteration of taste,” affirms Michele Y. Halyard, MD, in a commentary accompanying the Hong study (J Support Oncol. 2009;7:68-69). An associate professor of radiation oncology at the Mayo Clinic in Scottsdale, Ariz, Dr Halyard adds that taste recovery may take 6 to 12 months after head-and-neck radiotherapy.

Zinc and other heavy metals play a part in the physiology of taste function, and uncontrolled studies have shown zinc supplementation to improve taste abnormalities in people with head-and-neck cancer who were treated with external-beam radiation therapy. Dr Halyard and colleagues conducted a large randomized trial in which zinc did not help prevent or recover taste loss caused by radiation therapy, but, conflictingly, a small pilot trial demonstrated more promising results. Zinc’s specific role in taste perception is unknown, writes Dr Halyard, “but it is a recognized cofactor of alkaline phosphatase, which is the most abundant enzyme within the taste-bud membrane.”

Dr Halyard recommends that clinicians consider arranging a formal nutritional consultation for patients undergoing cancer treatment and initiating enteral feeding if necessary. “Nutritional intervention has been shown to improve not only quality of life in cancer patients but survival as well and should play an important role in the management of patients with alterations in taste and smell that impact oral intake,” she contends.

Odor Identification and Aversion
Sense of smell doesn’t appear to be as affected as sense of taste in cancer patients, note Dr Hong and colleagues. People with lung, ovarian, and breast cancers did not differ significantly from people without cancer in 1 test measuring smell sensitivity. In addition, radiotherapy administered to patients with oropharyngeal cancer did not significantly change their ability to recognize odors.

Nevertheless, chemotherapy and radiation have been found to be major causes of dysosmia. In 1 study of 40 individuals with breast cancer, most recovered their ability to identify odors and had increased smell acuity 6 to 9 months after radiotherapy treatment.

Abnormal taste and odor perception are building blocks to food aversion. Many cancer patients report that high-protein foods give off an unpleasant taste and odor. Red meat seems to be a particular culprit; patients appear better able to tolerate protein in the forms of fish, chicken, eggs, and cheese. High-fat foods, vegetables, chocolate, and caffeinated drinks also frequently make the food-aversion lists of people with cancer.

Another contributor to taste aversion is xerostomia, otherwise known as “dry mouth.” This condition occurs in cancer patients when radiation damage to the salivary glands diminishes saliva secretion. Xerostomia is strongly linked with taste alteration, particularly with the problem of metallic tastes or aftertastes.

Better Understanding Will Lead to Better Management
Dr Hong et al conclude that new management strategies are needed to help cancer patients resolve taste and odor malfunctions. In a separate statement announcing the study, coinvestigator Andrea Dietrich, professor of civil and environmental engineering at Virginia Tech and an expert on the taste and odor assessment of water among cancer patients, pointed out that one of the purposes of the study was to provide both researchers and clinicians with a better understanding of the types and causes of taste and odor dysfunctions so that they can develop treatments for these conditions and improve quality of life for their patients.